The primary objective of this KO1 Mentored Research Scientist Development Award application is to allow the candidate the opportunity to pursue an independent research career in medical rehabilitation research. The candidate has experience as an Occupational Therapist and has doctoral and postdoctoral training in the field of motor control. The candidate's long-term objective is to create an independent line of research that contributes to the understanding of mechanisms of locomotion and its recovery in individuals with MS. The short-term career goals are to test the association between pathologically relevant white matter damage, impairment measures and patterns of locomotion following an acute episode in multiple sclerosis (MS). These associations are critical to our understanding of how neuropathology and functional mobility are related and will further develop our understanding of the mechanisms involved in the recovery of locomotion. The proposed career development plan includes specific training to learn 1) the pathophysiology, treatment and rehabilitation of MS, 2) diffusion tensor imaging and magnetization transfer imaging analyses, 3) analyses of gait ataxia, and 4) design, statistical analyses, and execution of clinical studies. The specific aims of the proposed studies will test the general hypothesis that, in MS and following an acute exacerbation the pattern of white matter damage is predictive of locomotor recovery. The proposed studies will investigate: 1) whether specific white matter tract abnormalities that occur following an acute exacerbation of MS correlate with specific sensorimotor impairments and features of walking patterns, and 2) whether damage to specific white matter tracts (i.e., the corticospinal, dorsal column medial lemniscal and cerebellar tracts) can predict the recovery of locomotion after a relapse of MS. These studies will incorporate measures of diffusion tensor imaging and magnetization transfer MRI for the evaluation of white matter integrity; in addition, the PIs will evaluate sensorimotor impairments of sensation, strength, spasticity, and ataxia, and relate these to locomotor function. Results of the proposed studies will, for the first time, provide important insights into neural mechanisms of locomotion, as well as the role of specific white matter fiber tracts in the recovery of locomotion in people with multiple sclerosis. [unreadable] [unreadable] [unreadable]